Abstract

Antigen recognition through the T cell receptor (TCR) αβ heterodimer is one of the primary determinants of the adaptive immune response. Vaccines activate naïve T cells with high specificity to expand and differentiate into memory T cells. However, antigen-specific memory CD4 T cells exist in unexposed antigen-naïve hosts. In this study, we use high-throughput sequencing of memory CD4 TCRβ repertoire and machine learning to show that individuals with preexisting vaccine-reactive memory CD4 T cell clonotypes elicited earlier and higher antibody titers and mounted a more robust CD4 T cell response to hepatitis B vaccine. In addition, integration of TCRβ sequence patterns into a hepatitis B epitope-specific annotation model can predict which individuals will have an early and more vigorous vaccine-elicited immunity. Thus, the presence of preexisting memory T cell clonotypes has a significant impact on immunity and can be used to predict immune responses to vaccination.

Data availability

The sequencing data that support the findings of this study have been deposited on Zenodo (https://doi.org/10.5281/zenodo.3989144).

The following data sets were generated

Article and author information

Author details

  1. George Elias

    Laboratory of Experimental Hematology (LEH), University of Antwerp, Antwerp, Belgium
    For correspondence
    igeorgeelias@gmail.com
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8419-9544
  2. Pieter Meysman

    Biomedical Informatics Research Network Antwerp, Department of Mathematics and Informatics, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5903-633X
  3. Esther Bartholomeus

    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  4. Nicolas De Neuter

    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6011-6457
  5. Nina Keersmaekers

    Centre for Health Economics Research & Modeling Infectious Diseases, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  6. Arvid Suls

    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  7. Hilde Jansens

    Department of Clinical Microbiology, Antwerp University Hospital, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  8. Aisha Souquette

    Department of Immunology, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    No competing interests declared.
  9. Hans De Reu

    Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  10. Marie-Paule Emonds

    Histocompatibility and Immunogenetic Laboratory, Rode Kruis-Vlaanderen, Mechelen, Belgium
    Competing interests
    No competing interests declared.
  11. Evelien Smits

    Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  12. Eva Lion

    Laboratory of Experimental Hematology, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  13. Paul G Thomas

    Department of Immunology, St. Jude Children's Research Hospital, Memphis, United States
    Competing interests
    No competing interests declared.
  14. Geert Mortier

    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  15. Pierre Van Damme

    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  16. Philippe Beutels

    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  17. Kris Laukens

    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
  18. Viggo Van Tendeloo

    Laboratory of Experimental Hematology (LEH), Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
    Competing interests
    Viggo Van Tendeloo, is an employee of Johnson & Johnson since 1/11/2019 and remains currently employed at the University of Antwerp.
  19. Benson Ogunjimi

    Antwerp Unit for Data Analysis and Computation in Immunology and Sequencing, University of Antwerp, Antwerp, Belgium
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0831-2063

Funding

University of Antwerp

  • George Elias
  • Esther Bartholomeus
  • Nicolas De Neuter

Research Foundation Flanders

  • Pieter Meysman
  • Kris Laukens
  • Benson Ogunjimi

American Lebanese Syrian Associated Charities

  • Aisha Souquette
  • Paul G Thomas

National Institute of Allergy and Infectious Diseases

  • Aisha Souquette
  • Paul G Thomas

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Armita Nourmohammad, University of Washington, United States

Ethics

Human subjects: Protocols involving the use of human tissues were approved by the Ethics Committee of Antwerp University Hospital and University of Antwerp (Antwerp, Belgium), and all of the experiments were performed in accordance with the protocols

Version history

  1. Preprint posted: August 25, 2020 (view preprint)
  2. Received: March 14, 2021
  3. Accepted: January 7, 2022
  4. Accepted Manuscript published: January 25, 2022 (version 1)
  5. Accepted Manuscript updated: January 26, 2022 (version 2)
  6. Version of Record published: February 8, 2022 (version 3)

Copyright

© 2022, Elias et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. George Elias
  2. Pieter Meysman
  3. Esther Bartholomeus
  4. Nicolas De Neuter
  5. Nina Keersmaekers
  6. Arvid Suls
  7. Hilde Jansens
  8. Aisha Souquette
  9. Hans De Reu
  10. Marie-Paule Emonds
  11. Evelien Smits
  12. Eva Lion
  13. Paul G Thomas
  14. Geert Mortier
  15. Pierre Van Damme
  16. Philippe Beutels
  17. Kris Laukens
  18. Viggo Van Tendeloo
  19. Benson Ogunjimi
(2022)
Preexisting memory CD4 T cells in naïve individuals confer robust immunity upon hepatitis B vaccination
eLife 11:e68388.
https://doi.org/10.7554/eLife.68388

Share this article

https://doi.org/10.7554/eLife.68388

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